A Double-blind, Placebo-Controlled, Randomized, 4-Week, Multiple-Dose, Proof-of-Mechanism Study in Subjects with Early Alzheimer*s Disease Investigating the Effects of JNJ-54861911 on Aß Processing in CSF and Plasma

Completed

Conditions: 10029305
cognitive impairment
Early Alzheimers disease

Registration Number: NL-OMON40301

Lead Sponsor: Janssen-Cilag

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study unless otherwise specified:;1. Criterion Modified per amendment;1.1 Subjects with prodromal AD: Subject must be a man or woman between 50 and 90 years of age, inclusive.;Subjects who are asymptomatic at risk for AD: Subject must be a man or woman between 60 and 85 years of age, inclusive.;2. Criterion modified per amendment;2.1 Subjects must have had sufficient education or work experience to exclude mental retardation and must be able to read and write.;3. Criterion Modified per amendment;3.1 Subjects with prodromal AD: Subjects must have a CDR score of 0.5 consistent with MCI.;Subjects who are asymptomatic at risk for AD: Subjects must have a CDR score of 0 and as such rated as normal.;4. Criterion modified per amendment;4.1 Subjects must have evidence of amyloid deposition by means of either:;a) low CSF Aß1-42 levels at screening;b) a positive amyloid positron emission tomography (PET) amyloid scan at screening (optional depending on the site*s PET capability);;5. Subjects must have a body mass index (BMI=weight/height²) between 18 and 35 kg/m2, inclusive, at screening.;6. Before randomization, a woman must be not of childbearing potential: premenarchal; postmenopausal (>=50 years of age with amenorrhea for at least 12 months; permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy,;7. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partners should also use an appropriate method of birth control for at least the same duration.;8. Subjects must be otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening or at baseline. If there are abnormalities, they must be consistent with the underlying illness in the study population.;9. Subjects must be otherwise healthy or medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel [including liver enzymes, other specific tests], hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject*s source documents and initialed by the investigator.;10. Subjects must have a reliable informant (relative, partner, friend, *);11. Subject must be able to be compliant with self-administration of medication;12. Subject must be able to swallow drug as a whole.;13. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.;14. Subject must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study unless otherwise specified:;1. Criterion modified per amendment;1.1 Subject has evidence of any brain disease, other than potential very early signs of AD (e.g. mild hippocampal atrophy) or typical age related changes (e.g. mild white matter hyperintensity on MRI) or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that could explain a possible cognitive deficit (including, but not limited to vascular encephalopathy or strokes, as imaged by cerebral MRI and Major Depression, as defined by DSM-IV criteria).;2. Subject has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia):;Degenerative dementia such as: frontal lobe dementia, cortical basal dementia, progressive supranuclear palsy and primary progressive aphasia; dementia associated with significant Parkinsonism, e.g. Parkinson*s Disease, diffuse Lewy body disease; multi infarct dementia (vascular dementia,); primary and secondary brain tumor; genetic disorder associated with dementia (Huntington*s disease, Pick*s disease, fronto-temporal dementia, hereditary ataxias, early-onset familial AD); dementia due to sporadic or familiar forms of prion diseases , e.g. Creutzfeldt-Jakob disease; diffuse white matter disease; normal-pressure hydrocephalus; head injury leading to cognitive decline; recently diagnosed or untreated thyroid disease; vitamin B12 or folic acid deficiency; drug and medication intoxication; severe depression (pseudo dementia); chromosome 21 trisomy (Down Syndrome); neurosyphilis; HIV dementia;;3. Subject has evidence of familial autosomal dominant Alzheimer*s Disease;4. Subject has any contra-indications for MRI (prostheses, implants, claustrophobia, pacemakers, etc.);5. Subject has a clinically significant abnormal physical- or neurological examination, vital signs or 12-lead ECG (incl. QTc>450msec for males and females, Left Bundle Branch Block, AV Block second degree or higher, permanent pacemaker or implantable cardioverter defibrillator (ICD)) at screening or baseline (Day 1 predose), which in the opinion of the investigator is not appropriate and reasonable for the population under study.;6. Criteria modified per amendment;6.1. Subject has a relevant history of or current neurological disease other than asymptomatic at risk for AD/pAD/MCI (including any history of post-lumbar puncture headache), which in the opinion of the investigator may make interpretation of possible new neurological signs or symptoms difficult.;7. Criteria modified per amendment;7.1.Subject has a history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. instable situation needing monitoring or regular dose adaptations).;8. Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).;9. Subject has a history of spontaneous, prolonged or severe bleeding of unclear origin.;10. Criterion modified per amendment.;10.1. Subject has a history of epilepsy or fits or unexplained black-outs o

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objectives of this study are:<br /><br>• To determine the effect of JNJ-54861911 on the level of Aβ1-40 in CSF<br /><br>following 4 weeks of treatment in subjects with early AD, i.e., asymptomatic<br /><br>subjects at risk for AD and subjects with pAD at the intended target dose range;<br /><br>• To determine the effect of JNJ-54861911 on level of Aβ1-40 in plasma<br /><br>following 4 weeks of treatment in subjects with early AD at the intended target<br /><br>dose range.<br /><br>• To investigate the plasma PK and metabolism of JNJ-54861911 following 4 weeks<br /><br>of treatment in subjects with early AD;<br /><br>• To investigate the CSF exposure of JNJ-54861911 following 4 weeks of<br /><br>treatment in subjects with early AD;<br /><br>• To investigate the safety and tolerability of JNJ-54861911 after<br /><br>multiple-dose administration in the anticipated target dose range in subjects<br /><br>with early AD.</p><br>

Secondary Outcome Measures